The present invention relates to a composition containing peroxidic species or oxidation products, its method of preparation, and its use. More specifically, the invention relates to a two-component system of a pharmaceutical formulation which contains: peroxidic species or reaction products resulting from oxidation of an olefinic compound, in a liquid form or in a solution, by an oxygen-containing oxidizing agent; a penetrating solvent; a dye containing a chelated metal; and an aromatic redox compound. The invention also relates to the preparation of the pharmaceutical formulation and its use in treating coronary arteriosclerosis.
Ozone is a triatomic gas molecule and an allotropic form of oxygen. It may be obtained by means of an electrical discharge or intense ultraviolet light through pure oxygen. After the discovery of ozone by Christian Friedrich Schonbein in 1840, six decades passed without any interest in its medical utilization. At the beginning of World War I, Albert Wolf used the gas for the first time therapeutically when it was administered for the topical healing of infected wounds. However, development of medical applications was impeded by the discovery of antibiotic drugs (sulphonamides and penicillins) in the 1920s along with skepticism associated with the internal applications of ozone gas in the field of medicine. For sixty years, ozone clinical research had been limited to European private practice with anecdotal material not published in peer-reviewed journals. Moreover, the popular misconception that ozone is a serious pollutant, the xe2x80x9cfree radicalxe2x80x9d theory of disease, and the antioxidant supplement market have comprehensibly prejudiced medical orthodoxy against its use.
Ozone therapy is a misnomer. Ozone is an extremely reactive and unstable gas with mechanisms of action directly related to the by-products that it generates through selective interaction with organic compounds present in the plasma and in the cellular membranes. The selective reaction of ozone with unsaturated olefins occurs at the carbonxe2x80x94carbon double bond, generating ozonides. Ozone is toxic by itself, and its reaction products, ozonides, are unstable and are not therapeutic by themselves.
Hydrogen peroxide (H2O2), discovered in 1818, is present in nature in trace amounts. Hydrogen peroxide is unstable and decomposes violently (foams) when in direct contact with organic membranes and particulate matter. Light, agitation, heating, and iron all accelerate the rate of hydrogen peroxide decomposition in solution.
Hydrogen peroxide by direct contact ex vivo kills microbes that have low levels of peroxide-destroying enzymes, catalases. For instance, there is no bactericidal effect when hydrogen peroxide is infused into the blood of rabbits infected with peroxide-sensitive E. coli. Moreover, increasing the concentration of peroxide ex-vivo in rabbit or human blood containing E. coli produces no evidence of direct bactericidal activity. The lack of effect of high concentrations of hydrogen peroxide was directly related to the presence of the peroxide-destroying enzyme, catalase. To have any effect, high concentrations of hydrogen peroxide would have to be in contact with the bacteria for significant periods of time. Large amounts of hydrogen peroxide-destroying enzymes, such as catalase, normally present in the blood make it impossible for peroxide to exist in blood for more than a few seconds. One must conclude that hydrogen peroxide introduced into the blood stream by injection or infusion does not directly act as an extracellular germicide in blood or extracellular fluids.
However, hydrogen peroxide does participate in the bactericidal processes within activated macrophage cells. The critical therapeutic criteria for intracellular peroxidation are the selective delivery, absorption and activation of peroxidic carrier molecules into only diseased macrophages, which are believed to be incapable of upgraded catalase and glutathione reductase activity. Infused hydrogen peroxide is a generalized poison whereas targeted intracellular peroxidation is a selective therapeutic tool.
U.S. Pat. No. 4,451,480 to De Villez teaches a composition and method for treating acne. The method includes topically treating the affected area with an ozonized material derived from ozonizing various fixed oil and unsaturated esters, alcohols, ethers and fatty acids.
U.S. Pat. No. 4,591,602 to De Villez shows an ozonide of Jojoba used to control microbial infections.
U.S. Pat. No. 4,983,637 to Herman discloses a method to parenterally treat local and systemic viral infections by administering ozonides of terpenes in a pharmaceutically acceptable carrier.
U.S. Pat. No. 5,086,076 to Herman shows an antiviral composition containing a carrier and an ozonide of a terpene. The composition is suitable for systemic administration or local application.
U.S. Pat. No. 5,126,376 to Herman describes a method to topically treat a viral infection in a mammal using an ozonide of a terpene in a carrier.
U.S. Pat. No. 5,190,977 to Herman teaches an antiviral composition containing a non-aqueous carrier and an ozonide of a terpene suitable for systemic injection.
U.S. Pat. No. 5,190,979 to Herman describes a method to parenterally treat a medical condition in a mammal using an ozonide of a terpene in a carrier.
U.S. Pat. No. 5,260,342 to Herman teaches a method to parenterally treat viral infections in a mammal using an ozonide of a terpene in a carrier.
U.S. Pat. No. 5,270,344 to Herman shows a method to treat a systemic disorder in a mammal by applying to the intestine of the mammal a trioxolane or a diperoxide derivative of an unsaturated hydrocarbon which derivative is prepared by ozonizing the unsaturated hydrocarbon dissolved in a non-polar solvent.
U.S. Pat. No. 5,364,879 to Herman describes a composition for the treatment of a medical condition in a mammal, the composition contains a diperoxide or trioxolane derivative of a non-terpene unsaturated hydrocarbon which derivative is prepared by ozonizing below 35xc2x0 C. the unsaturated hydrocarbon in a carrier.
Despite the reports on the use of terpene ozonides for different medical indications, terpene ozonides display multiple deficiencies. For example, ozonides of monoterpene, such as myrcene and limonene, flamed out in the laboratory. Consequently, they would be too dangerous to formulate or store.
Furthermore, ozonides of geraniol, a linear monoterpene alcohol, in water or in DMSO did not show any clinical efficacy in three case of viral Varicella Zoster (shingles) and two cases of Herpes Simplex dermatitis.
Coronary heart disease (xe2x80x9cCHDxe2x80x9d) is the single largest killer in the U.S. It affects about 12 million people in this country. It is responsible for 1 out of 5 deaths, totaling nearly about half a million a year. The disease is caused by a narrowing of the large arteries by plaques made up of blood fats, such as cholesterol, smooth muscle cells, collagen and other proteins, and even calcium deposits. The narrowing of the arteries in turn hamper the supply of blood to the heart muscle. CHD can cause angina, which involves episodes of chest pain due to decrease supply of blood flow and oxygen to the heart muscle. About 6.3 million Americans suffer from angina. CHD can lead to myocardial infarctions, commonly known as heart attacks where tissues in portions of a heart die because of inadequate blood supply. This occurs when one of the coronary arteries becomes completely blocked. Heart attacks affect over 1 million of Americans each year. When the heart muscle is damaged, it has problems pumping blood efficiently, causing congestive heart failure, which affects about 5.6 million Americans. Then, about 4.3 million Americans have heart rhythm disturbances, which are known as arrhythmias.
There is, therefore, a pressing need for new and curative treatments for these diseases.